Quantifying the Electronic Effects of Carbohydrate Hydroxy Groups by Using Aminosugar Models

Abstract

Methyl amino-deoxy-glycosides with α- and β-gluco, α-galacto, or α-manno stereochemistry with the amino functionality in each of the four possible non-anomeric positions have been synthesized and their pK(a) values determined by titration. These model compounds were chosen because they are the amino derivatives of the most common glycosyl acceptors. From this study it was possible to evaluate the electron density at each of the given positions in the carbohydrate and compare them. Some general trends were observed: The basicity of the amino groups decreases in the order 6-NH(2)>3-NH(2)>2-NH(2)>4-NH(2) (referring to the position). The basicity of a of an amino-deoxy-sugar generally increases when one or more substituents on the sugar ring are axial. The basicity decreases when the amine is antiperiplanar to an oxygen atom. These findings are in agreement with the observations obtained from glycosylation chemistry and the regioselective protection of sugars.

Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity

“…[3] Ther eactivity of donor glycosides has been very well documented:t he relative reactivity value (RRV) of hundreds of thioglycosides has been established and hundreds of anomeric triflates and other covalent reactive species,key reactive intermediates formed in situ during the reaction, have been characterized. [5] At the same time,i ti sc ommon practice to change protecting groups on the acceptor building block to influence the yield or change the stereoselectivity of ag lycosylation reaction. [5] At the same time,i ti sc ommon practice to change protecting groups on the acceptor building block to influence the yield or change the stereoselectivity of ag lycosylation reaction.…”

Acceptor-influenced and donor-tuned base-promoted glycosylation

“…Obviously, the anomeric configuration in the acceptor structure has a noticeable effect on the glycosylation, resulting in lower oxyanion reactivity for methyl β-glycopyranosides. The considerable effect of the anomeric configuration on the reactivity of remote hydroxy groups may be rationalized by stereoelectronic effects [12]. Moreover, the lower reactivities of the methyl β-glycopyranosides may also be dependent on the decreased solubility of the partially deprotonated methyl β-glycospyranosides in the solvent used.…”

Biosynthesis of amino deoxy-sugar-conjugated flavonol glycosides by engineered Escherichia coli

“…1) and is involved in the therapeutic potential of the compounds [2]. The conjugation of amino sugars to an aglycone improves the basicity [35], alters the pharmacological properties [2,36,37], and also alters the mechanism of action of parent compound [38,39]. Moreover, the inherent positive charge of the amino sugar also enhances the solubility and potential for ionic interactions under normal physiological conditions [40,41].…”